This application addresses broad challenge area (04), clinical research, and specific challenge topic 05-CA-104, comparative effectiveness research on cancer treatment. One in six American men will be diagnosed with prostate cancer in their lifetime. While many experts agree that active surveillance is appropriate for most elderly patients with low-risk cancer, elderly patients with low-risk cancer often receive similarly aggressive cancer therapy as those with high-risk cancer, raising the concern of overtreatment. Radiation therapy is the most common cancer therapy used for elderly patients with localized prostate cancer. However, the medical necessity of this approach has not been established. Given the significant side effects and cost associated with radiation therapy and its wide application, it is critical to evaluate this treatment approach compared with conservative management to facilitate treatment decisions. The primary objectives of the study will be to define the prognosis of elderly patients with localized prostate cancer, in terms of overall and disease-specific survival, subsequent use of cancer therapies, and serious cancer-related complications, following radiation therapy compared to conservative management. This population-based study will use the Surveillance, Epidemiology, and End Results (SEER) data linked with Medicare claims to identify eligible patients diagnosed in 1992-2005. Because of its large sample size (about 140,000 men with up to 15 years of follow-up), this study will have ample statistical power. To minimize biases often associated with observational studies, this study will use an instrumental variable analytical approach, which has been applied successfully to mimic the results of randomized clinical trials using observational data. This proposed study will provide long-term outcome benchmarks critical for treatment decisions. When complete, this proposed study will provide the longest and largest analysis to date of longitudinal data on survival, use of subsequent cancer therapies, and prevalence of long-term serious cancer related complications among elderly patients with screen-detected localized prostate cancer treated with radiation therapy vs. conservative management. It is anticipated that the empirical outcomes data will help clarify any misconception about the potential benefit of radiation therapy and facilitate informed decision-making. Reducing the overutilization of radiation therapy could potentially result in cost savings exceeding 700 million dollars per year and improve the quality of life of many patients. Lay Description This study is to provide long-term data on various clinical outcomes following the two most commonly used treatment options for elderly patients with prostate cancer: deferred treatment and radiation therapy. The findings of this study will provide benchmark references to facilitate treatment decision- making. Reduction in overtreatment will result in substantial savings while improving the quality of life of millions of patients.